The genetic structure of Norway

The aim of the present study was to describe the genetic structure of the Norwegian population using genotypes from 6369 unrelated individuals with detailed information about places of residence. Using standard single marker- and haplotype-based approaches, we report evidence of two regions with distinctive patterns of genetic variation, one in the far northeast, and another in the south of Norway, as indicated by fixation indices, haplotype sharing, homozygosity, and effective population size. We detect and quantify a component of Uralic Sami ancestry that is enriched in the North. On a finer scale, we find that rates of migration have been affected by topography like mountain ridges. In the broader Scandinavian context, we detect elevated relatedness between the mid- and northern border areas towards Sweden. The main finding of this study is that despite Norway’s long maritime history and as a former Danish territory, the region closest to mainland Europe in the south appears to have been an isolated region in Norway, highlighting the open sea as a barrier to gene flow into Norway.Subject terms: Genetic variation, Genetic markers     

The past,present, and future of direct-to-consumer genetic tests

Technological advances in the field of human genetics have resulted in a wave of discoveries of common DNA sequence variants that are associated with a risk of common complex diseases, such as heart attack, that account for a substantial proportion of morbidity, mortality, and health care costs in most contemporary populations. The overall predictive power of these sequence variants can be considerable, due to the high incidence of these diseases and the sheer number of associations that have been discovered. Health care providers have been slow to utilize this knowledge for preventative medicine. However, several companies have taken on a translational role by offering genetic tests based on these discoveries direct to consumers. In this paper, we review the current state and future prospects of such genetic tests, as scientists involved both in the discovery of disease associations and the development of genetic tests.     

治疗性单克隆抗体药动学相互作用的风险评估策略

生物制剂可用于治疗各种疾病,包括肿瘤、风湿、胃肠道疾病、皮肤科疾病、呼吸道疾病、激素缺乏症和感染。尽管近来批准了很多生物制品,但有关其药物间相互作用临床研究还不多。单克隆抗体是最主要的一类治疗性生物制品,本文介绍评价其药物间相互作用的风险评估策略,指出了评估中的关键因素,并建议将相互作用风险评估作为治疗性生物制品综合药物开发的一部分。     

Collective self-esteem and the onset of chronic conditions and reduced activity in a longitudinal study of aging

Collective self-esteem (CSE) is an individual's self-evaluation as a member of social groups. It is thought to promote health and well-being in later life by moderating the harmful effects of losing personal control over these experiences. In this study of 144 community-dwelling older adults in Manitoba, Canada, among those with lower health-related perceived control, respondents with higher CSE at baseline developed significantly fewer chronic conditions over the next 6 years. An expected negative relationship between age and activity level, which respondents higher in CSE showed, was not observed among respondents with lower CSE, whose activity level in the sample age range (78-98 years) was already very low. Higher CSE thus appeared to delay the decline of activity and chronic health that would otherwise accompany age and the absence of perceived control.     

Factors associated with delivery complications in rural Bangladesh

Objectives There are only a few studies on maternal morbidity, delivery complications and maternal mortality in Bangladesh. This study analyzes data from a follow-up study conducted by the Bangladesh Institute of Research for Health and Technologies (BIRPERHT) on maternal morbidity in rural Bangladesh in 1993. Methods A total of 1020 pregnant women were interviewed in the follow-up component of the study. The survey collected information on socioeconomic and demographic characteristics, pregnancy-related care and practice, morbidity during the period of follow-up as well as in the past, information concerning complications at the time of delivery and during the postpartum period. For the purpose of this study, we selected 993 pregnant women with at least one antenatal follow-up. Both bivariate and multivariate analyses were conducted to identify the potential risk factors for complication during delivery and duration of labor. Results and conclusions It appears that complications during the antenatal period can result in various complications at the time of delivery. Some of the important findings are: hemorrhage during the antenatal period increases the risk of excessive hemorrhage during delivery, the risk of obstructed labor increases significantly if abdominal pain is observed during the antenatal period, prolonged labor appears to be significantly higher for the first pregnancy, and pregnancies suffering from abdominal pain during pregnancy tend to have a higher risk of prolonged labor during delivery. The duration of labor appears to be negatively associated with the number of previous pregnancies, being longest for the first pregnancies. The duration of labor pain is significantly higher for the respondents who reported the index pregnancy as undesired, and, similarly, the respondents who were reported to be involved with gainful employment would have a shorter duration of labor pain than those having no involvement with gainful employment.     

雷公藤红素对IL-1和IL-2活性及PGE2释放的抑制作用

雷公藤红素0.1～1.0μg/ml在试管内能降低LPS诱导的小鼠腹腔巨噬细胞外和细胞内白细胞介素-1(IL-1)的活性,也能抑制ConA诱导的小鼠脾细胞产生白细胞介素-2(IL-2).动态观察表明,雷公藤红素经预处理8h和3h后已能分别抑制IL-1和IL-2的产生。此外,雷公藤红素能降低A23187刺激家兔滑膜细胞释放前列腺素E₂(PGE₂)。     

Randomized phase II trial of gemcitabine and either day 1 or day 8 carboplatin for advanced non‐small‐cell lung cancer: Is thrombocytopenia predictable?

Aim:   Two 21-day gemcitabine–carboplatin schedules were evaluated in patients with advanced non-small cell lung cancer in order to assess the effect of timing of the carboplatin dose on toxicity and efficacy.
Methods:   Patients were randomized to gemcitabine (1000 mg/m² on days 1 and 8 of a 21-day cycle) and carboplatin (AUC 5, on day 1) (Carbo d1 arm) or the same gemcitabine schedule with carboplatin given on day 8 (Carbo d8 arm). Twenty patients with Stage IIIB or IV non-small-cell lung cancer were enrolled in each arm.
Results:   The achieved dose intensities of both gemcitabine and carboplatin were significantly higher in the Carbo d1 arm. The total rates of grade 3 or 4 hematological and non-hematological toxicities (any toxicity, any cycle) were 80% and 65%, respectively, with no significant differences between the two arms. Nine patients in the Carbo d1 arm, but only one patient in the Carbo d8 arm, required a platelet transfusion. There were 10 partial responses (four Carbo d1 arm, six Carbo d8 arm), giving an overall response rate of 25% (95% CI 13–41%).
Conclusion:   Administration of carboplatin on day 8 of this regimen confers no clear advantage compared with day 1 carboplatin, with similar toxicity but lower dose intensity. A formula for the prediction of thrombocytopenia is proposed.